Allogeneic hematopoietic cell transplantation (HCT) is curative therapy for many hematologic diseases, but development of serious immune mediated disorders after transplantation limits greater success. Although some immune mediated disorders are very rare (< 1%), others such as acute and chronic grafl-versus-host disease (GVHD) are more common (30-50%) and cause high morbidity and mortality. Project 1 is a longitudinal study with the aim of better characterizing the incidence, characteristics, and outcomes of these disorders. We particularly focus on three syndromes with high morbidity and mortality: cutaneous sclerosis, bronchiolitis obliterans syndrome (BOS) and persistent, recurrent or late-onset acute GVHD (late acute GVHD). These syndromes have distinct clinical characteristics and respond poorly to currently available therapies. Based on our current knowledge about potential pathophysiology and response to treatments, we propose biomarker studies and clinical trials of targeted agents elsewhere in the grant proposal. Project 1 will enroll approximately 1000 patients before allogenic HCT who will be followed for two years to collect detailed data about any immune mediated disorders of interest that arise. In addition, research samples will be obtained to provide longitudinal biologic material on affected cases and samples from controls. We will use a subset of these research samples to validate and extend three biomarker models: the Ferrara model of 4 proteins associated with early acute GVHD, the Schultz model of 4 biomarkers associated with chronic GVHD, and the Weissinger urine proteomic patterns associated with acute and chronic GVHD. Since the criteria for positive and negative samples have been determined, we will be able to select purely informative the models. Project 1 is synergistic but not overlapping with a U01 funded observational trial limited to patients with chronic GVHD (2007-2012)